Label-free optical sensors based upon surface structured photonic crystals have recently been demonstrated as a highly sensitive method for performing a wide variety of biochemical and cell-based assays. See, e.g., Cunningham, et al., Label-Free Assays on the BIND System. Journal of Biomolecular Screening, 2004. 9:481-490. These sensors reflect only a narrow band of wavelengths when illuminated with white light at normal incidence, where positive shifts of the reflected peak wavelength value (PWV) indicate the adsorption of detected material on the sensor surface. See, e.g., Cunningham, et al., Colorimetric resonant reflection as a direct biochemical assay technique. Sensors and Actuators B, 2002. 81:316-328. By spatially confining incident photons at the resonant wavelength, a high optical field is generated at the sensor surface that extends a short distance into a test sample, much like an evanescent field. The high degree of spatial confinement of resonant photons within the device structure leads to a strong interaction between the structure and adsorbed biomaterial, and to the ability to perform high resolution imaging of protein and cell attachment. See, e.g., Li, et al., A new method for label-free imaging of biomolecular interactions. Sensors and Actuators B, 2004. 99:6-13.
Previously, photonic crystal optical biosensors have been fabricated from continuous sheets of plastic film using a process in which the periodic surface structure is replicated from a silicon master wafer using a UV-cured polymer material. See, e.g., Cunningham, et al., A plastic colorimetric resonant optical biosensor for multiparallel detection of label-free biochemical interactions. Sensors and Actuators B, 2002. 85:219-226. This patterned polymer can be subsequently coated with a high refractive index TiO2 layer that is generally thinner than the height of the surface structure. Such devices have been demonstrated for a wide variety of biochemical and cell-based assays, with a mass density sensitivity resolution less than 0.1 pg/mm2 and a large dynamic range enabling single cell detection. See, e.g., Lin et al., A label-free biosensor-based cell attachment assay for characterization of cell surface molecules. Sensors and Actuators B, Accepted April 2005. In general, optimization of device sensitivity requires increasing the interaction of the electromagnetic field intensity distribution with the molecules deposited atop the photonic crystal surface. Therefore, selection of optical materials and design of the surface structure topology is aimed at extending the electromagnetic field profile from the interior regions of the photonic crystal (where they cannot interact with adsorbed material) to the region adjacent to the photonic crystal that includes the liquid test sample.
Methods are needed in the art to increase the sensitivity of these and other types of sensors and to decrease the cost of their manufacture.